Interaction Between Cd9 And Pi3k-P85 Activates The Pi3k/Akt Signaling Pathway In B-Lineage Acute Lymphoblastic Leukemia

ONCOLOGY REPORTS(2021)

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摘要
Our previous study has shown that CD9 knockdown could suppress cell proliferation, adhesion, migration and invasion, and promote apoptosis and the cytotoxicity of chemotherapeutic drugs in the B-lineage acute lymphoblastic leukemia (B-ALL) cell line SUP-B15. In this study, we further investigated the molecular mechanism underlying the effects of CD9 on leukemic cell progression and the efficacy of chemotherapeutic agents in B-ALL cells. Using the CD9-knockdown SUP-B15 cells, we demonstrated that the silencing of the CD9 gene significantly reduced the expression of phosphorylated-phosphatidylinositol-3 kinase (p-PI3K), phosphorylated-protein kinase B (p-AKT), P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1), breast cancer resistance protein (BCRP), matrix metalloproteinase 2 (MMP2) and phosphorylated-focal adhesion kinase (p-FAK). In addition, glutathione S-transferase (GST) pull-down assay showed the binding between CD9 and both PI3K-p85 alpha and PI3K-p85 beta in vitro, while co-immunoprecipitation assay showed the binding between CD9 and both PI3K-p85 alpha and PI3K-p85 beta in vivo. Furthermore, the PI3K/AKT inhibitor LY294002 mirrored the effects of CD9 knockdown in SUP-B15 cells. Taken together, these findings demonstrated that CD9 activates the PI3K/AKT signaling pathway through direct interaction with PI3K-p85 in B-ALL cells. Our data provide evidence for the inhibition of the PI3K/AKT pathway as a novel therapeutic option in CD9 antigen-positive B-ALL.
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关键词
B-lineage acute lymphoblastic leukemia, CD9, PI3K-p85, PI3K, AKT signaling pathway, SUP-B15 cells
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